The present invention relates to a method and a device for controlling the flow and spatial distribution of dry medication powder being deposited on a substrate in a dose forming process, and more specifically by using an electric iris diaphragm/shutter (a diaphragm which is also operable as a shutter) in forming pre-metered doses particularly of finely divided dry medication electro powder.
The dosing of drugs is carried out in a number of different ways in the medical service today. Within health care there is a rapidly growing interest in the possibility of acting dosing systemic medication drugs as a powder directly to the airways and lungs of a patient by means of an inhaler in order to obtain an effective, quick and user-friendly administration of such substances.
A dry powder inhaler, DPI, represents a device intended for administration of powder into the deep or upper lung airways by oral inhalation. For systemic delivery of medication drugs a deep lung deposition is used, but for local treatment of the airways the objective is local deposition, not deep lung. With deep lung should be understood the peripheral lung and alveoli, where direct transport of active substance to the blood can take place. In order for a particle to reach into the deep lung the aerodynamic particle size should typically be less than 3 xcexcm, and for a local lung delivery typically less than 5 xcexcm. Larger particle sizes will easily stick in the mouth and throat, which underlines the importance of keeping the particle size distribution of the dose within tight limits to ensure that a high percentage of the dose actually is deposited in the deep lung upon inhalation when the objective is systemic delivery of a drug. Furthermore, the inspiration must take place in a calm manner to decrease air speed and thereby reduce deposition in the upper respiratory tracts.
To succeed with systemic delivery of medication powders to the deep lung by inhalation there are some criteria, which have to be fulfilled. It is for instance very important to obtain a high dosing accuracy in each administration to the user. A very high degree of de-agglomeration of the medication powder is also of great importance. This is not possible with dry powder inhalers of today without special arrangements as for example a so-called spacer.
Powders for inhalers have a tendency of agglomerating, in other words to clod or to form smaller or larger lumps, which then have to be de-agglomerated. De-agglomeration is defined as breaking up agglomerated powder by introducing electrical, mechanical, or aerodynamic energy. Usually de-agglomeration is performed in at least two stages: stage one is in the process of depositing powder while building up the dose and stage two is in the process of dispersing the powder during the patient""s inspiration of air through the DPI.
The term electro-powder refers to a finely divided medication powder presenting controlled electric properties being suitable for administration by means of an inhaler device. Such an electro-powder provides possibilities for a better dosing from equipment using a technique for electric field control such as disclosed in our U.S. Pat. No. 6,089,227 as well as our Swedish Patents No. 9802648-7 and 9802649-5, which present excellent inhalation dosing performance. The state of the art also discloses a number of solutions for depositing powder for dosing. The International Application WO 00/22722 presents an electrostatic sensing chuck using area matched electrodes. U.S. Pat. No. 6,063,194 discloses a powder deposition apparatus for depositing grains on a substrate using an electrostatic chuck having one or more collection zones and using an optical detection for quantifying the amount of grains deposited. U.S. Pat. Nos. 5,714,007 and 6,007,630 disclose an apparatus for electrostatically depositing a medication powder upon predefined regions of a substrate, the substrates being used to fabricate suppositories, inhalants, tablet capsules and the like. In U.S. Pat. Nos. 5,699,649 and 5,960,609 are presented metering and packaging methods and devices for pharmaceuticals and drugs, the methods using electrostatic photo technology to package microgram quantities of fine powders in discrete capsule and tablet form.
A common difficulty encountered when using electrostatic technology and/or electrical fields in combination with electrostatic charging of the powder particles in a deposition process, is to remove the charge of the particles and the charge of the substrate, if an isolator, as the particles are being deposited on the substrate for forming the dose. If the removal of charges is incomplete or takes too long it will affect the forming of the dose negatively in that the charged particles already deposited will present a local repelling electric field, which tends to stop newly attracted particles from settling on the targeted area of the substrate and forces newcomers to settle at the outskirts of the target area. The repelling field grows in strength as more particles are deposited on the target area. Finally, the field is so strong that further deposition is not possible even if the net field strength at some distance from the target area is exerting an attractive force on the charged particles.
In cases where electrostatic chucks are used, regardless of whether the chuck substrate, normally of a dielectric material, is pre-charged in the deposition area or areas to create the necessary local electric field in the target area(s), or a system of electrodes are used to attract the charged particles or if a combination of pre-charging and electrodes are used, it is always difficult to fill the target area with the correct amount of particles, because the repelling field grows stronger with every particle deposited, leading to a spreading out of particles over a larger area than the intended target area. This is also true where the target area, the deposition area, is beads, which are captured and held by the chuck by for instance electrostatic force during the deposition of particles onto the beads themselves. It is thus often impossible to form doses of sufficient mass and suitable spatial shape. Often, the chuck principle also requires powders of predetermined or known specific charge (xcexcC/g) in order to predict the mass of particles attracted to the chuck, which in itself presents a big challenge.
Further, prior art technology devices seldom reach a sufficiently high degree of de-agglomeration, and an exact dose with a low relative standard deviation (RSD) between doses is not well controlled. This is partly due to difficulties in controlling the production line parameters during production of the doses, partly due to shortcomings in the design of the inhaler device, which makes it hard to comply with regulatory demands. The difficulties leave much to be desired when it comes to dose conformity and lung deposition effectiveness of the medication substance. Therefore, there is still a demand for pre-fabricated high accuracy pre-metered doses to be loaded into an inhaler device, which then will ensure repeated and exact systemic or local pulmonary delivery of doses administered by inhalation.
A method and a device are defined for controlling the transfer of charged particles of a medication powder emitted from a particle generator to a defined target area of a substrate in a dose forming process. A particle transfer electrode is arranged for forming an electric iris diaphragm and shutter with an electric field associated for the transfer of the powder particles from the particle generator to the defined target area of a substrate to carry a pre-metered powder dose, thereby to control the direction and speed of particles in the dose forming process. The electric iris diaphragm/shutter is located between the particle generator and the substrate such that all particles must pass the iris diaphragm for being transferred to the substrate. This iris diaphragm is also operating as a shutter. By adjusting amplitude and frequency of a superimposed AC potential charged particles will oscillate in the created AC field such that only small light particles emerge from the iris diaphragm/shutter for further transfer in the dose forming process. Furthermore by the adjustment of amplitude and frequency a majority of charged particles emerging are accelerated and retarded in synchronism with the AC field, such that they impact on a defined target area of the substrate with a low speed and momentum resulting in a desired dose porosity.